Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder
Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder
复制标题
DOI：
10.1073/pnas.1217750110
复制
发表时间：
2013-05-14
影响因子：
11.1
通讯作者：
Binder, Elisabeth B.
中科院分区：
文献类型：
--
作者：
Mehta, Divya;Klengel, Torsten;Binder, Elisabeth B.
儿童时期的虐待可能影响基本的生物过程，并留下持久的表观遗传标记，导致成年后的不良健康后果。本研究旨在探讨不同早期环境对创伤后应激障碍（PTSD）患者外周血细胞中疾病相关基因表达和DNA甲基化的影响。与相同的创伤暴露对照组（n = 108）相比，具有相似临床症状和匹配的成人创伤暴露但不同儿童期不良事件的PTSD患者（n = 32和29）的基因表达谱几乎完全不重叠（98%）。个体转录物水平上的这些差异被群体之间几个不同生物网络的丰富所掩盖。此外，这些基因表达的变化伴随着并可能由相同基因座中DNA甲基化的变化介导，在儿童期虐待组（69%）中的比例远远高于非儿童期虐待组（34%）。这项研究是独一无二的，它提供了全基因组证据，表明在存在或不存在儿童期虐待的情况下，PTSD发生了不同的生物学修饰。研究结果表明，不重叠的生物学途径似乎在两个创伤后应激障碍组中受到影响，而DNA甲基化的变化似乎在儿童期虐待组中产生了更大的影响，这可能反映了创伤后应激障碍的病理生理学差异，取决于暴露于儿童期虐待。这些结果有助于更好地了解创伤暴露对应激相关精神疾病病理生理过程的影响程度，并可能对个性化医疗产生影响。
Childhood maltreatment is likely to influence fundamental biological processes and engrave long-lasting epigenetic marks, leading to adverse health outcomes in adulthood. We aimed to elucidate the impact of different early environment on disease-related genome-wide gene expression and DNA methylation in peripheral blood cells in patients with posttraumatic stress disorder (PTSD). Compared with the same trauma-exposed controls (n = 108), gene-expression profiles of PTSD patients with similar clinical symptoms and matched adult trauma exposure but different childhood adverse events (n = 32 and 29) were almost completely nonoverlapping (98%). These differences on the level of individual transcripts were paralleled by the enrichment of several distinct biological networks between the groups. Moreover, these gene-expression changes were accompanied and likely mediated by changes in DNA methylation in the same loci to a much larger proportion in the childhood abuse (69%) vs. the non-child abuse-only group (34%). This study is unique in providing genome-wide evidence of distinct biological modifications in PTSD in the presence or absence of exposure to childhood abuse. The findings that nonoverlapping biological pathways seem to be affected in the two PTSD groups and that changes in DNA methylation appear to have a much greater impact in the childhood-abuse group might reflect differences in the pathophysiology of PTSD, in dependence of exposure to childhood maltreatment. These results contribute to a better understanding of the extent of influence of differences in trauma exposure on pathophysiological processes in stress-related psychiatric disorders and may have implications for personalized medicine.